The purpose of these experiments is to increase our general understanding of the cellular mechanisms of the immune response. The general phenomenon of lymphocyte (T cell - B cell) interactions will be explored. Whether or not organisms respond to a particular antigenic stimulus, by producing humoral antibodies, is genetically controlled by immune response (Ir) genes. One class of these genes is linked to the major histocompatibility locus, H-2, in mice. The human analogue is the HL-A histocompatibility system. The mechanism of non-response by mice to some antigens in unknown. It is also unknown whether T cells and B cells can only interact if they are of the same H-2 type. We propose experiments to help answer these two questions. The system we plan to use is that of allophenic (tetraparental) mice in which T cells and B cells of two different histocompatibility types can be combined. The two populations of cells are also chosen so that responder and non-responder cells (to particular antigens) are combined. The basic understanding of T cell - B cell interactions and the control of such interactions by immune response genes is vital for a complete understanding of the mechanism of the immune response. This in turn is vital for the understanding of allergy, cancer, and rejection of organ transplants.